So, let's look at where it all begins, the primary organs of the immune system. Now, here, we have one of the lymphatic system, but the lymphatic system we'll look at again in the next section when we look at the secondary lymphoid system. But this shows you where the thymus is, and I think you can probably also figure out more or less where the bone marrow is. The bone marrow is the primary organ that produces most of the immune cells in your body, and it has, of course, parallels with the bursa of fabricius in birds. So, let's go into a picture of the bone marrow. What we've got in here is a picture of all of the different kinds of cells that are in the bone marrow. Now, there's a bunch of them here that we're just not going to look at right now, but I want to point out that a lot of the bone marrow is made out of fat. Usually, you tend to think of fat as being some kind of let's say inactive storage cell. But the fat at the bone marrow is a cell type that sends out a lot of the signals that regulate hematopoiesis or the development of blood cells. It makes sense because the amount of fat you have will essentially signal your nutritional status and let the cells know just exactly how much energy they have to keep going. Now, the bone marrow is the location of the hematopoietic stem cells, and you don't even see one in here because, of course, they are few and far between given their ability to regenerate and then produce everything. It is the site of the production of lymphoid cells. So, here we have, let's see, I don't think we've got lymphoid cells in this. We've got myelocytes in it. That is the myeloid stem cell population. Some of them have developed into, you can see, a red blood cell progenitor eosinophils, and a variety of other cell types. But just as a reminder, this is where the NK cells arise, and this is where the B cells rearrange their genes as part of their development. Also, T cells will start out here, but they're going to migrate into the thymus to rearrange their genes. So, it's primarily the bone marrow of the femur, the humerus, arm bones, hip bones, and sternum that do the production of most of your blood cells. Here is a picture that shows you, again, the location of the thymus. The thymus is the region where the T cells rearrange their genes. So, we've got three primary lymphoid organs: bursa, bone marrow, and thymus. The thymus is the rearrangement site for the T cells. Now, here's a really old classic picture of the thymus. In this one, you can see that it's got a cortex or outer layer, and an inner layer, the medulla. So, those are just general words meaning outer layer and inner layer. The T cells are going to start out coming in in the outer layer. So, they're going to start on the outside and work their way in. The T cell progenitors will come in in a relatively undifferentiated state. They will rearrange these cells for their receptors to produce a variety of cell types that can recognize antigen. The cells are then checked still in the outside to determine whether or not they can also recognize a MHC molecule, which is going to be critically important to their function. If they pass that test, they begin migrating towards the inside. Now, some of this next stage begins a little bit earlier on, but primarily, the medulla region of the thymus is the place where cells undergo negative selection. The first selection that these cells experience is something we call positive selection. That's in the cortex, and that's to make sure that they can identify antigen on an MHC molecule. The second stage, negative selection, takes place inside in the medulla, and a corresponding process happens with B cells. This stage will get rid of T cells that recognize your own self antigens. That's particularly important for Th cells because if we can do a good job of cleaning these guys out in the medulla, then we'll see it's going to be much easier to dump down a stray misbehaving cell later on when you're trying to prevent auto-immune diseases. So, the selection process, the process goes first from rearranging genes, and a lot of cells die off in that because they don't make a productive rearrangement, positive selection, that is, you go through and make sure that the T cells combined MHC. Then negative selection in the interior to make sure that they can't recognize your own self antigens. Cells that pass that test leave in the circulation and head out to coordinate your immune response. Cells that fail any of these tests will die, and well over 95 percent will undergo apoptosis as part of this process. Now, once they've survived it however, they're going to head out into the secondary lymphoid organs to figure out what's going on in your body.